10-69104641-G-T

Variant names:

• chr10-69104641-G-T
• rs7377
• NM_002727.4:c.*521G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002727.4(SRGN):​c.*521G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,320 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (348 hom., cov: 32)
  • Exomes 𝑓: 0.057 (0 hom.)
• Consequence: SRGN NM_002727.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 7 publications found

Genes affected

SRGN (HGNC:9361): (serglycin) This gene encodes a protein best known as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of many hematopoietic cells also contain a protease-resistant peptide core, which may be important for neutralizing hydrolytic enzymes. This encoded protein was found to be associated with the macromolecular complex of granzymes and perforin, which may serve as a mediator of granule-mediated apoptosis. Two transcript variants, only one of them protein-coding, have been found for this gene. [provided by RefSeq, Jul 2010]

ENSG00000297237 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002727.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGN	NM_002727.4	MANE Select	c.*521G>T		3_prime_UTR	Exon 3 of 3	NP_002718.2
	SRGN	NM_001321053.2		c.*521G>T		3_prime_UTR	Exon 4 of 4	NP_001307982.1
	SRGN	NM_001321054.1		c.*521G>T		3_prime_UTR	Exon 2 of 2	NP_001307983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGN	ENST00000242465.4	TSL:1 MANE Select	c.*521G>T		3_prime_UTR	Exon 3 of 3	ENSP00000242465.3
	SRGN	ENST00000718456.1		c.*521G>T		3_prime_UTR	Exon 3 of 3	ENSP00000520834.1
	ENSG00000297237	ENST00000746408.1		n.336-662C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9524 AN: 152064 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0571 AC: 8 AN: 140 Hom.: 0 Cov.: 0 AF XY: 0.0333 AC XY: 3 AN XY: 90

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 14

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0678 AC: 8 AN: 118

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0626 AC: 9520 AN: 152180 Hom.: 348 Cov.: 32 AF XY: 0.0634 AC XY: 4718 AN XY: 74382

African (AFR) AF: 0.0559 AC: 2322 AN: 41512

American (AMR) AF: 0.0759 AC: 1160 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3472

East Asian (EAS) AF: 0.109 AC: 565 AN: 5180

South Asian (SAS) AF: 0.143 AC: 686 AN: 4812

European-Finnish (FIN) AF: 0.0344 AC: 364 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0610 AC: 4149 AN: 68010

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0580 Hom.: 50

Bravo AF: 0.0634

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.72
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7377; hg19: chr10-70864397;